A leading cause of death in the United States today is coronary artery disease, in which atherosclerotic plaque causes blockages in the coronary arteries, resulting in ischemia of the heart (i.e., inadequate blood flow to the myocardium). The disease manifests itself as chest pain or angina. In 1996, approximately 7 million people suffered from angina in the United States.
Coronary artery bypass grafting (CABG), in which the patient's chest is surgically opened and an obstructed artery replaced with a native artery harvested elsewhere, has been the conventional treatment for coronary artery disease for the last thirty years. Such surgery creates significant trauma to the patient, requires long recuperation times, and causes a great deal of morbidity and mortality. In addition, experience has shown that the graft becomes obstructed with time, requiring further surgery.
More recently, catheter-based therapies such as percutaneous transluminal coronary angioplasty (PTCA) and atherectomy have been developed. In PTCA, a mechanical dilatation device is disposed across an obstruction in the patient's artery and then dilated to compress the plaque lining the artery to restore patency to the vessel. Atherectomy involves using an end effector, such as a mechanical cutting device (or laser) to cut (or ablate) a passage through the blockage. Such methods have drawbacks, however, ranging from re-blockage of dilated vessels with angioplasty to catastrophic rupture or dissection of the vessel during atherectomy. Moreover, these methods may only be used for that fraction of the patient population where the blockages are few and are easily accessible. Neither technique is suitable for the treatment of diffuse atherosclerosis.
A more recent technique which holds promise for treating a larger percentage of the patient population, including those patients suffering from diffuse atherosclerosis, is referred to as transmyocardial revascularization (TMR). In this method, a series of channels are formed in the left ventricular wall of the heart. Typically, between 15 and 30 channels about 1 mm in diameter and up to 3.0 cm deep are formed with a laser in the wall of the left ventricle to perfuse the heart muscle with blood coming directly from the inside of the left ventricle, rather than traveling through the coronary arteries. Some researchers believe that the resulting channels improve perfusion of the myocardium with oxygenated blood. Apparatus and methods have been proposed to create such channels both percutaneously and intraoperatively (i e., with the chest opened).
U.S. Pat. No. 5,389,096 to Aita et al. describes a catheter-based laser apparatus for use in percutaneously forming channels extending from the endocardium into the myocardium. The catheter includes a plurality of control lines for directing the tip of the catheter. As the laser ablates the tissue during the channel forming process, the surrounding tissue necroses, resulting in fibroid scar tissue surrounding the channels. U.S. Pat. No. 5,380,316 to Aita et al. describes an intraoperative laser-based system for performing TMR.
U.S. Pat. No. 5,591,159 to Taheri describes mechanical apparatus for performing TMR comprising a catheter having an end effector formed from a plurality of spring-loaded needles. The catheter first is positioned percutaneously Within the left ventricle. A plunger is then released so that the needles are thrust into the endocardium. The needles core out small channels that extend into the myocardium as they are withdrawn. The patent suggests that the needles may he withdrawn and advanced repetitively at different locations under fluoroscopic guidance. The patent does not appear to address how tissue is ejected from the needles between the tissue-cutting steps
Although it is generally agreed that TMR benefits many patients, researchers do not agree upon the precise mechanism by which TMR provides therapeutic benefits. One theory proposes that TMR channels remain patent for long periods of time, and provide a path by which oxygenated blood perfuses the myocardium. However, relatively recent histological studies indicate that TMR channels may close within a short time following the procedure. For example, Fleischer et al., in “One-Month Histologic Response Of Transmyocardial Laser Channels With Molecular Intervention,” Ann. Soc. Thoracic Surg., 62:1051-58 (1996), evaluated histologic changes associated with laser TMR in a 1-month nonischemic porcine model, and was unable to demonstrate channel patency 28 days after TMR.
Other researchers have observed that in laser-based TMR patients, there appears to he enhanced vascularization of the tissue on the margins of the scar tissue resulting from the laser channel-forming process. It has therefore been hypothesized that the act of causing trauma to portions of the myocardium may invoke a regenerative process, that enhances the development of neovascularization and endothelialization in the tissue.
To investigate these alternative theories, researchers have studied the use of gene therapy in promoting blood vessel growth in the tissue surrounding laser TMR channels. In one study, researchers intraoperatively administered a single dose of vascular endothelial growth factor (VEGF) at the time of laser TMR. Although the study showed no significant increase in myocardial vascularity, the researchers hypothesized that a longer duration of VEGF residence may be necessary to stimulate angiogenesis.
In view of the foregoing, it would be desirable to provide apparatus and methods for stimulating revascularization and tissue growth in an interior region of an organ or vessel, such as the heart, by stimulating native revascularization and tissue growth mechanisms.
It would also be desirable to provide apparatus and methods for stimulating revascularization and tissue growth by controlling the placement and size of tissue treatment sites, thereby resulting in a controlled degree of scar tissue formation.
It would be still further desirable to provide apparatus and methods for stimulating revascularization and tissue growth by depositing a controlled amount of a bioactive agent, such as an angiogenic growth factor, at the treatment sites.